Elevated exosome-transferrable lncRNA EPB41L4A-AS1 in CD56bright NK cells is responsible for the impaired NK function in neuroblastoma patients by suppressing cell glycolysis

Wenjia Chai; Xiaolin Wang; Zhengjing Lu; Shihan Zhang; Wei Wang; Hui Wang; Chenghao Chen; Wei Yang; Haiyan Cheng; Huanmin Wang; Jun Feng; Shen Yang; Qiliang Li; Wenqi Song; Fang Jin; Hui Zhang; Yan Su; Jingang Gui

doi:10.1016/j.clim.2023.109322

Elevated exosome-transferrable lncRNA EPB41L4A-AS1 in CD56^bright NK cells is responsible for the impaired NK function in neuroblastoma patients by suppressing cell glycolysis

Clin Immunol. 2023 May:250:109322. doi: 10.1016/j.clim.2023.109322. Epub 2023 Apr 5.

Authors

Wenjia Chai¹, Xiaolin Wang¹, Zhengjing Lu¹, Shihan Zhang², Wei Wang¹, Hui Wang¹, Chenghao Chen³, Wei Yang⁴, Haiyan Cheng⁴, Huanmin Wang⁴, Jun Feng⁴, Shen Yang⁴, Qiliang Li⁵, Wenqi Song⁵, Fang Jin⁵, Hui Zhang¹, Yan Su², Jingang Gui⁶

Affiliations

¹ Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China.
² Medical Oncology Department, Pediatric Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, China.
³ Department of Thoracic Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
⁴ Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China.
⁵ Department of Clinical Laboratory Center, Beijing Children's Hospital, Capital Medical University, National Center for Children Health, Beijing 100045, China.
⁶ Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China. Electronic address: guijingang@bch.com.cn.

PMID: 37024023
DOI: 10.1016/j.clim.2023.109322

Abstract

NK cells are one of key immune components in neuroblastoma (NB) surveillance and eradication. Glucose metabolism as a major source of fuel for NK activation is exquisitely regulated. Our data revealed a diminished NK activation and a disproportionally augmented CD56^bright subset in NB. Further study showed that NK cells in NB presented with an arrested glycolysis accompanied by an elevated expression of the long noncoding RNA (lncRNA) EPB41L4A-AS1, a known crucial participant in glycolysis regulation, in the CD56^bright NK subset. The inhibitory function of lncRNA EPB41L4A-AS1 was recapitulated. Interestingly, our study demonstrated that exosomal lncRNA EPB41L4A-AS1 was transferrable from CD56^bright NK to CD56^dim NK and was able to quench the glycolysis of target NK. Our data demonstrated that an arrested glycolysis in patient NK cells was associated with an elevated lncRNA in CD56^bright NK subset and a cross-talk between heterogeneous NK subsets was achieved by transferring metabolic inhibitory lncRNA through exosomes.

Keywords: Exosome; Glycolysis; LncRNA; NK cell subset; Neuroblastoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD56 Antigen
Exosomes* / metabolism
Glycolysis
Humans
Killer Cells, Natural
Neuroblastoma* / genetics
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism

Substances

CD56 Antigen
RNA, Long Noncoding
NCAM1 protein, human